A basic question in developmental biology is how an initially unspecified sheet of cells organizes itself. Based on relative position, cells differentiate to generate widely diverse forms and patterns. We are exploiting the genetics of the fruit fly, Drosophila, to understand the molecular and cellular mechanisms by which cells organize themselves within the segment. Systematic genetic screens have identified the segment polarity genes, which mediate the cell interactions that establish, maintain and refine the organization within every segment. patched (ptc) is a segment polarity gene whose deduced amino acid sequence suggests that it encodes a large integral membrane protein. Genetic experiments suggest that it functions as a receptor. We will use the cloned ptc gene and other cloned segment polarity genes as tools to study the interactions that organize cells within the segment. The specific aims of the proposed experiments are: 1) To determine whether a combinatorial code of segment polarity gene expression predicts morphological determination within the segment. 2) To confirm and extend the description of the interactions which organize cells within the segment. What are the signalling pathways that organize the segment? 3) To determine the minimum number of cells of required to generate the complete pattern. 4) To ask how ectopic expression of ptc will redirect the segmental pattern. 5) To determine the subcellular location of the ptc protein product and its topology within the membrane. Are the physical properties of the ptc protein consistent with its functions as determined above? 6) To identify other genes which act in the same or antagonistic signalling pathways (e.g., ligands, second messengers) by their genetic interactions with ptc. Understanding the cellular phenomena which organize cells within the insect segment will answer a basic question in developmental biology and will ultimately help us to understand developmental disorders in man.